The training of a dentist scientist encompasses postdoctoral specialized clinical training, advanced basic science, and thesis research experience. The clinical training will include diagnosis and treatment of patients with the complete scope of oral and maxillofacial problems. The training will culminate in specialty certification in Oral and Maxillofacial Surgery. The advanced basic science preparation will include graduate level courses, seminars, laboratory meetings and attendance and presentations at research meetings. Graduate coursework will include core classes in Microbiology-Immunology, Biochemistry, Molecular Biology, Oral Biology and Statistics, as well as other courses chosen to fit the specific needs of the trainee's program. Thesis research experience will include laboratory rotations and the thesis research project. The thesis project will examine the regulation of differential gene expression in the pathogenesis of the opportunistic fungus, Candida albicans. Virulence in Candida strains has been correlated with several factors which include but are not limited to: the ability to form hyphae, the synthesis of proteases and the ability to adhere to a number of host surfaces. We hypothesize that expression of specific genes is associated with these virulence factors and that the expression of some of these genes may depend upon interaction with host factors. The aim of this study will be to isolate and characterize some of these genes and ultimately to examine the regulation of their expression, particularly those involved in the blastospore-hyphae transition. Stage specific cDNA libraries will be prepared from blastospores and hyphae grown under several conditions, and then screened with mRNA probes from both stages; those cDNAs whose expression is differentially regulated in these two forms will be further characterized. In many pathogenic organisms, it has been shown that the spectrum of proteins expressed in the human host during infection are significantly different from those obtained from cells cultured in vitro. We will therefore prepare Candida mRNA from pseudomembranous plaques collected directly from the oral cavities of patients and screen the cDNA from this material by differential hybridization. Isolates obtained from patients will be simultaneously cultured under in vitro conditions for blastospore and hyphal production. Unique cDNAs expressed in material isolated directly from patients will be given increased priority for further characterization to assess the effect of the host component interaction. The knowledge gained from these studies can be used to dissect the host-parasite interaction in oral candidiasis. Drs. John and Deborah Greenspan will serve as collaborators. Dr. Leonard Kaban will serve as the mentor for the clinical training in Oral and Maxillofacial Surgery, Dr. Caroline Damsky for the research component, and Dr. Nina Agabian will direct the thesis research. The excellent working relationship between the three mentors will assure a focused, integrated program of postgraduate education leading to both a Ph.D. degree in oral biology and postgraduate specialty certification in the chosen field and provide the necessary background to pursue a career in academic dentistry.